Objective The aim of the study was to describe the characteristics of otherwise healthy children with obstructive sleep apnea (OSA; OSA-I) and children with OSA and obesity (OSA-II) treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in 2019 in France. Design National cross-sectional survey. Patients Children with OSA-I and OSA-II. Main outcome measures Initiation criteria, age, adherence, equipment and settings Results Patients with OSA-I and OSA-II represented 6% (n=84, 71% males) and 10% (n=144, 72% males) of the national cohort, respectively. The apnea-hypopnea index (63% vs 76%), alone or combined with nocturnal gas exchange (25% vs 21%, for OSA-II and OSA-I patients respectively) were used as initiation criteria of CPAP/NIV. OSA-II patients were older at CPAP/NIV initiation (mean age 11.0±4.0 vs 6.8±4.5 years, p<0.001) and were treated for a longer time (2.3±2.6 vs 1.3±1.5 years, p=0.008) than OSA-I patients. NIV was used in 6% of OSA-I patients and 13% of OSA-II patients (p=0.142). Nasal mask was the most used interface in both groups. Mean CPAP level was higher in OSA-II patients as compared to OSA-I patients (8.7±2.0 vs 7.7±2.4 cmH 2O, p=0.02). Objective compliance was comparable (mean use 6.8±2.6 vs 5.9±3.0 hours/night in OSA-I and OSA-II, respectively, p=0.054). Conclusion Six and 10% of children treated with long term CPAP/NIV in France in 2019 had OSA-I and OSA-II, respectively. Both groups were preferentially treated with CPAP and were comparable except for age, with OSA-II patients being older.

Medication Utilization and Lung Function Changes

Introduction This study aimed to describe the epidemiology and etiologies of critical respiratory diseases of ex-premature infants (EPIs) admitted to pediatric intensive care unit (PICU). In addition, we described the outcomes and resources used of EPIs and identified associated factors for mortality of these infants. Materials and Methods Infants ≤2 years old with acute respiratory illnesses admitted to PICU of Vietnam National Children’s Hospital from November 2019 to April 2021 were enrolled. We compared respiratory pathogens, outcomes, and PICU resources utilized between term infants and EPIs. Univariate followed by multivariable regression analysis were used to evaluate the association between risk factors and mortality. Results Among 1,183 patients aged ≤2 years were admitted for critical respiratory illness, 202 (17.1%) were EPIs. Respiratory viruses were detected in 53.5% and 38.2% among EPIs and term infants, respectively. Compared to term infants, a higher proportion of EPIs required mechanical ventilation (MV) (66.5 vs. 85.6%, p<0.005) and vasopressor support (10.7 vs. 37.6%, p<0.005). EPIs had a longer median duration of PICU stay (11.0 [IQR: 7; 22] vs. 6.0 days [IQR: 3; 11], p=0.09), hospital stay (21.5 [IQR: 13; 40] vs. 10.0 days [IQR: 5; 18], p<0.005) and case fatality rate (31.3% vs. 22.6%) compared to term infants. In EPIs, PIM3 score [ (aOR): 1.51; 95% (CI): 1.30-1.75] and PELOD2 score at admission (aOR: 1.41; 95% CI: 1.08-1.85) were associated with mortality. Conclusion EPIs with critical respiratory illnesses constituted a significant population in the PICU and required more PICU support and had worse clinical outcomes compared to term infants.

Central apneas are a prevalent yet complex phenomenon, particularly among children. This retrospective study, conducted over a decade (from 2012 to 2022), analyzed central apneas in a cohort of 612 pediatric patients who underwent ventilation at the Sleep Medicine and Long-Term Ventilation Unit of the Bambino Gesù Children’s Hospital in Rome, Italy. Among this group, 67 patients met the inclusion criteria for central apneas. Central apneas often arise within the context of various underlying pathologies, including neurological disorders, genetic syndromes, and brain tumors. We categorized patients into three main groups including patients with “exclusively central apneas”, “predominantly central apneas”, and “predominantly obstructive apneas”. Ventilation modes were diverse, with pressure-controlled ventilation and pressure support being commonly used, reflecting the individualized nature of therapy. The choice of ventilation mode has been influenced by the underlying diagnosis and the severity of central apneas, with pressure support ventilation being the most frequently employed mode. Continuous Positive Airway Pressure was also employed in select cases. A statistically significant reduction (p<0.05) in mean cAHI was observed in patients with multimalformation syndromes, hypoxic-ischemic encephalopathy and Prader-Willi Syndrome. The reduction in mean cAHI was not statistically significant in the case of patients with brain tumors. While non-invasive ventilation was commonly used, invasive mechanical ventilation was selectively employed in more severe cases. The study highlights the need for personalized therapeutic strategies when managing central apneas in pediatric patients.

Introduction The aims of this study were to update our experience with biodegradable polydioxanone (PDO) airway stents in children focusing on effectiveness and safety, and to analyse the factors involved in the different outcomes observed. Materials and methods Retrospective study of patients managed with PDO stents from 2012 to 2023. Variables collected: demographics, comorbidities, indication , clinical baseline, stent size, location, complications, clinical outcome, and time of follow-up. Statistical analyses were performed in order to detect the eventual contribution of variables in the different outcomes observed. Results 54 PDO stents were placed in 26 patients (median age, 4 m). All showed severe symptoms of central airway obstruction due to: tracheomalacia 9 patients, bronchomalacia 5, tracheobronchomalacia 10, and tracheal stenosis 2. Stent placement was uneventful in every case: 29 stents in the trachea and 25 in main bronchi. 53,8% of patients needed successive stenting and all exhibited comorbidities. Complete clinical resolution was observed in 8 cases (30.7%), partial improvement in 13 (50%), unchanged in 4 (15.3%), and worsen in one. Age had a significant positive impact in outcome (6 months vs 3 m.; p=0.024). Additionally, smaller stents were associated with a better outcome (20 vs 26 mm; p=0.044). Granulation tissue was the most frequent complication (34.6%). Five patients (19.2%) died due to severe comorbidities, follow-up was complete in survivors (median, 58 m). Conclusions PDO stents are safe and effective when dealing with severe tracheobronchial obstruction. Stent-related granulation tissue continues to be a relevant matter of concern. This issue together with increased degradation times deserve further research.

BACKGROUND: Three-dimensional (3D) printing has become increasingly affordable. Several research projects used 3D printing to create in vitro upper airways model. However, studies using a mainstream desktop 3D printer never performed geometric validation of their model. The aim of this study was to perform geometric validation of a pediatric upper airways model printed with a mainstream desktop 3D printer. METHODS: Head computerized tomography (CT) scan of a 10-month-old female underwent segmentation between airways and surrounding anatomical structures. Airways segmentation allowed their measurement for further comparison with printed model. Head segmentation enabled the creation of a 3D printable volume file. To proceed to the geometric validation of the head model, the latter underwent a CT scan. Similar segmentation work was performed on the printed model for comparison. Overlap proportion between the original infant volume and the printed model as well as an average Hausdorff distance were calculated after manual alignment between the original and printed model. RESULTS: Volumes were 12.31 cm 3 and 12.32 cm 3 for the pediatric and the printed model upper airways, respectively (0.08% difference). Dice coefficient of original and printed model was 92%. The average Hausdorff distance was 0.21 mm. CONCLUSION: Desktop mainstream 3D printers can generate pediatric upper airway model with a high dimensional accuracy, as evidenced by our comprehensive geometrical validation.

Objective: We sought to characterize point-of-care lung ultrasound (LUS) findings in children with asthma exacerbations and to determine whether the presence and magnitude of findings were associated with asthma severity. Methods: We enrolled a convenience sample of patients aged 5-18 years presenting with acute asthma exacerbation to a tertiary care pediatric emergency department. Severity of an asthma exacerbation (mild, moderate, severe) was assessed within 1-hour of the LUS using the Hospital Asthma Severity Score, a validated asthma assessment tool. LUS was performed by trained pediatric emergency providers . The presence of LUS findings (any B-lines, ≥3 B-lines per view, consolidations, pleural effusion and pleural line abnormalities) was assessed using a standardized criterion. Results: A total of 111 patients with a median age of 8 years (IQR 6, 12) were enrolled. LUS was positive in 57% of patients. Pleural line abnormalities were observed in 34%, B-lines in 29%, consolidations <1cm in 24%, and consolidations ≥1cm in 7 %. Patients with moderate and severe asthma exacerbations were more likely to have any B-lines (31% and 43%, respectively) than patients with mild exacerbations (12%; p= 0.021), however the presence of ≥3 B-lines did not differ across severity groups. The presence of other findings did not differ based upon asthma severity. Conclusions: LUS findings are commonly observed in patients presenting with asthma exacerbations. While B-lines were more likely to be found in exacerbations of higher severity, LUS findings associated with pediatric pneumonia did not correlate with severity. These findings provide valuable information for the diagnostic use of LUS.

Abstract: Aim: Recent literature has shown epidemiological changes in bronchiolitis with an increased incidence in the post-SARS-CoV-2 pandemic period but reports regarding disease severity are conflicting. We aimed to describe the epidemiology, disease severity, and microbiology of bronchiolitis during the 2022-2023 cold season compared to the previous five years. Methods: This single-center retrospective observational study at IRCCS Gaslini, Italy, included all children aged 0-2 years hospitalized for bronchiolitis from September 1st, 2017, to August 31, 2023. Findings from the 2022-2023 season were compared to the previous five years. Results: We observed a statistically significant increase in the 2022-2023 season in the absolute number of bronchiolitis admissions. Children who required mechanical ventilation dramatically increased from a total of 7 patients in the previous five seasons to 17 in the 2022-2023 season alone ( p=0.001). All other severity parameters significantly increased: the need for respiratory support ( p=0.002) , the median length of stay (5 vs. 4, p=0.001), and the median duration of respiratory support (4 vs. 3, p=0.016). Conclusions: We report a substantial increase in the severity of bronchiolitis in the season 2022-2023 with a remarkable number of previously healthy infants requiring mechanical ventilation. Our data represents a call in our setting for urgent measures to plan prophylactic and therapeutic strategies and prepare healthcare systems. Further studies are needed to confirm whether our findings are an isolated phenomenon or part of a true global trend. Health systems need to be prepared and protective preventive measures should be implemented for all newborns.

Primary ciliary dyskinesia is a rare genetic ciliopathy characterized by impaired clearance of the airway, leading to recurrent airway infections and various pulmonary conditions. The underlying cause of PCD is complex and involves diverse mechanisms. On one hand, advancements in genetic analysis techniques have significantly contributed to identifying the mutated genes associated with PCD, which in turn, can aid in understanding the variable clinical presentations of the disease. On the other hand, based on the mutated gene, disease manifestation may change and this makes it more challenging to establish a standardized diagnosis approach. Hence, it is important to approach it with a comprehensive perspective. In this study, 8 Turkish individuals with PCD were subjected to whole-exome sequencing (WES) analysis, as well as other diagnostic tests such as ciliary beat frequency measurement, immunofluorescence staining (IF), and confocal microscopy. The findings from this study not only contribute to the enlightenment of PCD aetiology but also emphasize the importance of a multidisciplinary approach when diagnosing and understanding this complex genetic disorder.

Background: Vitamin D may contribute to the balance in between regulatory and suppressive functions of T cells to modulate the inflammatory process in asthma. Objective: To assess serum vitamin D levels and their relationship with asthma control, asthma severity and its anti-inflammatory effect in children. Methods: This systematic review was based on articles published between 2009 and August 2022. Children under 18 years old with asthma were included. Results: The initial database search identified 2,015 manuscripts. Through screening identified only 25 eligible articles, but only eight studies met criteria for inclusion in the meta-analysis. The analysis revealed that in six studies involving 588 participants, mean 25-hydroxyvitamin D levels were lower in children with uncontrolled asthma compared to those with controlled asthma, with a mean difference of -5.07 (-8.57, -1.57) and a high rate of heterogeneity I 2 = 89%. In five studies comprising 362 patients, the relationship between vitamin D and asthma severity was assessed. Lower levels of vitamin D were associated with a higher risk of severe asthma in children, with a mean difference of -6.00 (-8.09, -3.90) and substantial heterogeneity (90%, p<0.00001). In most patients, no significant correlation was found between vitamin D and lung function. Furthermore, serum vitamin D showed an association with interleukins and with regulatory T lymphocytes. Conclusion: Vitamin D plays a critical role in reducing asthma attacks. However, more randomized studies are necessary for a thorough evaluation and definitive recommendation for vitamin D supplementation.

Introduction: Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in cystic fibrosis (CF) patients from Tasmania and Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report epidemic P. aeruginosa (AUST-03) strains in South African CF patients at a public academic hospital detected during a previous study and characterise the resistomes. Methods: The P. aeruginosa AUST-03 (ST242) strains were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multi-locus sequence typing and resistome characterisation was performed using public databases. Core single nucleotide polymorphism phylogenies were performed on P. aeruginosa ST242 strains from the study and from public databases. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. Results: A total of 11 P. aeruginosa AUST-03 strains were isolated from two children with CF who had pulmonary exacerbations. The majority of the P. aeruginosa AUST-03 strains (8/11) were multidrug resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the strains. The P. aeruginosa AUST-03 (ST242) study strains were most closely related to strains from Canada, China, Denmark and Slovenia. Conclusion: Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing patient segregation and infection control strategies to prevent further spread and outbreaks.

Childhood interstitial lung disease associated with connective tissue disease and immune mediated is the second most common chILD diagnostic category. As knowledge of the molecular and genetic underpinnings of these rare disorders advances, the recognized clinical spectrum of pulmonary manifestations that can be associated with them continues to broaden. This review will focus on chILD and other pulmonary complications associated with primary immune disorders, namely monogenic inborn errors of immunity as well as acquired systemic autoimmune and autoinflammatory diseases. Pulmonary complications, including ILD in these diseases can confer increased risk for morbidity and mortality and can be complex to manage due to the multiple organ systems that can be impacted in these systemic disorders. Thankfully, pulmonologists do not have to work alone. These diseases often have stereotypical patterns of extra-pulmonary features which aid in their recognition. In collaboration with a multidisciplinary team of subspecialists, the pulmonary and other systemic manifestations can be managed effectively together. The goal of this review is to familiarize the reader with the distinct patterns of ILD and associated systemic/immunologic features that are characteristic of monogenic inborn errors of immunity and systemic autoimmune and autoinflammatory diseases. In addition, this review will highlight current, emergent and innovative therapeutic strategies and will underscore the important role of multidisciplinary management to improving outcomes for these patients.

Pediatric sleep-related breathing disorders, or sleep-disordered breathing (SDB), cover a range of conditions including obstructive sleep apnea (OSA), central sleep apnea (CSA), sleep-related hypoventilation disorders, and sleep-related hypoxemia disorder. Pediatric SDB is often underdiagnosed, potentially due to difficulties associated with performing the gold standard polysomnography (PSG) in children. This scoping review aims to: 1) provide an overview of the studies reporting on safe, noncontact monitoring of respiration in young children; 2) describe the accuracy of these techniques, and 3) highlight their respective advantages and limitations. PubMed and EMBASE were searched for studies researching techniques in children <12 years old. Both quantitative data and the quality of the studies were analyzed. The evaluation of study quality was conducted using the QUADAS-2 tool. A total of 17 studies were included. Techniques could be grouped into bed-based methods, ultra-wideband (UWB) radar, Doppler radar, video, infrared (IR) cameras, garment-embedded sensors, and sound analysis. Most either measured respiratory rate (RR) or detected apneas; five aimed to do both. Noncontact sleep monitoring techniques are safe, but accuracy data of these techniques is limited, and large heterogeneity exists regarding study quality and stage. Motion artifacts affect accuracies of apnea detection. Sleep respiration analysis could benefit from sleep stage classification and breathing sound analysis. Further research is crucial to facilitate easily accessible and safe non-contact methods for respiration monitoring in a home setting.

Background Cystic fibrosis (CF) related diabetes affects up to half of all adults with CF and is associated with higher morbidity and mortality. Our aim is to co-design an ideal model of care that integrates diabetes technology and better meets the needs of adults living with the condition to improve attendance, engagement, service satisfaction and clinical outcomes. Methods Using qualitative research methods, we evaluated disease perceptions, barriers and enablers to optimal CF-related diabetes management and service delivery. Integration of continuous glucose monitoring (CGM) was also explored. An initial broad purposive consumer survey was followed by focus groups with end-users. Grounded theory approach was utilized with major problem-areas identified then explored, coded and grouped into requisites for an ‘ideal model of care’ for adults living with CF-related diabetes. Results Two key themes emerged i) CGM was acceptable for use in adults with CF-related diabetes with many perceived benefits and should be integrated into the model of care, ii) an ideal model of care consisted of a dual-specialty service co-led by endocrinology and CF physicians and supported by diabetes nurse educator and CF dietitian with a goal to provide consistent and personalized diabetes management. Barriers to optimizing glycaemic control included diet, finger-prick testing, reduced access to CGM and pulmonary exacerbations. End-user feedback on CGM was overwhelmingly positive with regards to user operability. CGM was also identified as a tool that could be used to engage, educate and empower adults living with CF-related diabetes and facilitate constructive and personalized clinical decision-making by healthcare providers. Conclusion For adults living with CF, a diagnosis of diabetes is associated with increased treatment burden. End-users agreed CGM had many benefits and should be integrated into an ‘ideal model of care’ for CF-related diabetes that was co-led by endocrinology services integrated within a pre-existing CF service.

Introduction: The clinical spectrum of SARS-CoV-2 infection is well-established. However, understanding its long-term implications, especially in infants, remains limited. We aimed to evaluate pulmonary function tests in infants (iPFT) several months after a documented SARS-CoV-2 infection. Methods: An observational case-control study was performed. iPFT results in infants with persistent respiratory complaints several months after a SARS-CoV-2 infection were compared to a registry of patients assessed at our center between 2008 and 2019 using the Mann–Whitney U and Fisher’s exact tests. Excluded from the study were infants with chronic diseases and extreme prematurity. Results: iPFT data from sixteen infants with respiratory complaints and a history of SARS-CoV-2 infection and 475 controls were evaluated in the study. The median time between the SARS-CoV-2 infection and iPFT evaluation was 5.5 months (IQR=2.8-8.0). There were no differences between cases and controls in clinical characteristics and reason for iPFT evaluation. iPFT results showed no significant differences between cases and controls in lung volumes, compliance, or resistance. Expiratory airflow limitation was observed in both groups, with better low lung volume flows in the SARS-CoV-2 group. Categorization according to iPFT physiologic alteration and bronchodilator responsiveness were similar in the two groups. Conclusion: This study provides the first comprehensive iPFT data in infants following a SARS-CoV-2 infection. The findings suggest that SARS-CoV-2 infection does not cause unique long-term effects on pulmonary function in infants with chronic respiratory symptoms. Further studies in larger cohorts, particularly in infants with severe acute SARS-CoV-2 infection, are warranted to validate these findings.

Ventilator associated respiratory tract infections (VARTI) are among the most common indications for hospitalization among children with chronic respiratory failure requiring at-home ventilation. This review aims to provide an overview of the key clinical features, diagnostic approaches, and management strategies for home VARTIs while highlighting the challenges in diagnosis and management.

Objective: Acute bronchiolitis, primarily caused by Respiratory syncytial virus (RSV), is the most common cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity. We aim to evaluate the association between C-reactive protein (CRP) levels at admission and disease severity in children hospitalized due to RSV bronchiolitis. Study design: This single center retrospective cohort study included children (0-24 months old) who were hospitalized due to RSV bronchiolitis (January 2018 – March 2022) with CRP levels taken upon admission. Clinical data and severity parameters were extracted using MD-clone platform and the clinical research unit at SUMC. Results: 1,874 children (mean age of 6.7 months, 59% males) with a median CRP level of 1.92mg/dL were included. Children with elevated CRP (>1.92mg/dL) were significantly older (5.1 vs. 3.8 months, p<0.001), had higher rates of pneumonia (9.4% vs. 4.3%, p<0.001 ), urinary tract infection (UTI), (2.2% vs. 0.2%, p<0.001), acute otitis media (AOM), (1.7% vs 0.2%, p<0.001), admissions to pediatric intensive care unit (PICU) (7.4% vs 3.7%, p<0.001), antibiotic treatment (49.8% vs 37.2%, p<0.001) and longer hospitalizations (3.83 vs 3.31 days, p=0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk of 11.6, 2.25, 1.98, 1.44, respectively, p<0.001)). CRP thresholds of 3.51, 1.9, and 2.81 mg/dL for PICU admission, UTI, and pneumonia, were calculated using Youden’s index with AUC of 0.72, 0.62, and 0.61, respectively. Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Introduction: Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this quality improvement project was to implement a systematic gross motor assessment in children with CF ages 4-12 years. Methods: Physical therapists aimed to evaluate at least 50% of eligible children at our CF Center over 1 year using the Bruininks-Oseretsky Test of motor Proficiency, second edition (BOT-2), a norm referenced assessment for gross motor skills, with delays defined by scores less than 18 th percentile. Demographic and clinical data including body mass index, hospitalizations, genotype, and comorbidities were collected. Basic descriptive statistics summarized patient information. Parametric and non-parametric methods compared groups of interest. Linear regression assessed associations between BOT-2 measures and clinical characteristics. Results: Of the 105 eligible children, 72 (69%) completed the BOT-2 over 1 year. Forty-five (62.5%) scored below average in at least one category. Impaired strength (22.2%) was most common, followed by impaired balance (16.7%), running speed and agility (15.3%), and bilateral coordination (8.3%). Eleven (15.5%) scored below average on their total motor composite score (TMC). Increased age, comorbidities and hospitalizations were associated with a lower TMC. Conclusions: The BOT-2 was successfully implemented as part of routine CF care to screen for gross motor delays. Results suggest that a high percentage of children with CF, especially older children with comorbid conditions or a history of hospitalization, have impaired gross motor function. These findings support the need for routine gross motor evaluations and physical therapy interventions within pediatric CF clinics.